In Eucaryotes, normal development as opposed to neoplastic growth entails the orderly differentiation of cells within a narrowly defined temporal and spatial framework. A central feature of the development, in renal essence, is the process of cell differentiation. Homothallism, inherited switch of the mating type locus (MAT) in bakers yeast, saccharomyces cerevisiae, is exploited as a model system to study the mechanisms involved in differentiation of cell types. Yeast cell types are controlled by two allelic forms of the mating type locus, a and alpha. These cell types vary in cell surface properties, production and response to MAT specific pheromones, control of the differentiation events such as sporulation, budding pattern and a number of other characteristics. Homothallic strains can change these cell types by genetic alterations at MAT locus in a non-random fashion as often as every cell generation. The switches at MAT (a to alpha and alpha to a) are inherited in a simple Mendelian fashion. Since the cells can alternate between a and alpha, they must carry information for both loci. Preliminary evidence supports that switching is brought about by genetic rearrangements of the MAT loci. The experiments proposed in this application focus on the genetic approaches to study: (1) the molecular mechanism of MAT switching and (2) the controls of MAT in regulating various cell characteristics. This proposal stresses the genetic approach, but the final understanding must come from a combination of genetic and biochemical approaches.